Ward M M
Palo Alto Veterans Affairs Medical Center, California 94304, USA.
J Clin Epidemiol. 1996 Oct;49(10):1161-9. doi: 10.1016/0895-4356(96)00178-3.
Observational studies and meta-analyses of controlled clinical trials have been used to identify which measures of rheumatoid arthritis activity are most sensitive to change. These analyses often pool studies of different drugs, although it is not known if arthritis activity measures are differentially responsive to different drugs. In meta-analyses, estimates of the relative sensitivity to change of different measures may also be confounded by differences in drug efficacy, if studies of different drugs contribute different measures to the meta-analysis. To determine if the type of treatment acts as an important effect modifier or confounder in studies of the relative sensitivity to change of arthritis activity measures, we computed effect sizes for four measures (weighted tender joint count, grip strength, duration of morning stiffness, and erythrocyte sedimentation rate) used in each of 16 trials of five different disease-modifying antirheumatic drugs (methotrexate, sulfasalazine, cyclosporin A, intramuscular gold, and D-penicillamine) in rheumatoid arthritis. In a complete factorial analysis of variance, effect sizes differed significantly among drugs (p = 0.0006), but differed only marginally among measures (p = 0.08). No interaction was detectable between drugs and measures. These results suggested that effect modification by drugs was not present, but that pooled estimates of the sensitivity to change of different measures may be confounded in meta-analyses, if trials of more efficacious drugs contribute different measures than trials of less efficacious drugs. In a similar analysis of 26 trials of nine nonsteroidal anti-inflammatory drugs, we found significant differences in effect sizes among measures (p < 0.0001), but no differences among drugs (p = 0.96), and no interaction between drugs and measures. This study suggests that pooled analyses of the relative sensitivity to change of arthritis activity measures based on trials of different disease-modifying drugs may be confounded by drug effects, but confounding by drug effects is unlikely if these meta-analyses are based on trials of different nonsteroidal anti-inflammatory drugs. Although the power of these analyses to detect small interaction effects was limited, effect modification by drugs was not observed, indicating that the measures we examined were not strongly differentially responsive to different drugs.
观察性研究以及对照临床试验的荟萃分析已被用于确定类风湿关节炎活动的哪些指标对变化最为敏感。这些分析常常汇总不同药物的研究，尽管尚不清楚关节炎活动指标对不同药物的反应是否存在差异。在荟萃分析中，如果不同药物的研究对荟萃分析贡献了不同的指标，那么不同指标对变化的相对敏感性估计可能也会因药物疗效的差异而混淆。为了确定在关节炎活动指标对变化的相对敏感性研究中，治疗类型是否作为重要的效应修饰因素或混杂因素，我们计算了五种不同改善病情抗风湿药（甲氨蝶呤、柳氮磺胺吡啶、环孢素A、肌肉注射金和青霉胺）在16项类风湿关节炎试验中每项所使用的四种指标（加权压痛关节计数、握力、晨僵持续时间和红细胞沉降率）的效应量。在完全析因方差分析中，效应量在药物之间存在显著差异（p = 0.0006），但在指标之间仅有微小差异（p = 0.08）。未检测到药物与指标之间的相互作用。这些结果表明不存在药物的效应修饰作用，但如果疗效较好的药物试验与疗效较差的药物试验贡献了不同的指标，那么在荟萃分析中不同指标对变化的敏感性汇总估计可能会被混淆。在对九种非甾体抗炎药的26项试验进行的类似分析中，我们发现指标之间的效应量存在显著差异（p < 0.0001），但药物之间无差异（p = 0.96），且药物与指标之间无相互作用。本研究表明，基于不同改善病情药物试验的关节炎活动指标对变化的相对敏感性汇总分析可能会因药物效应而混淆，但如果这些荟萃分析基于不同非甾体抗炎药的试验，则不太可能因药物效应而混淆。尽管这些分析检测小的相互作用效应的能力有限，但未观察到药物的效应修饰作用，这表明我们所研究的指标对不同药物的反应差异不大。
